NCT03234140

Constitutional Genetics in Follicular Lymphoma

Constitutional Genetics to Predict Prognostic and Somatic Alterations in Follicular Lymphoma

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 1,883 (estimated)
• Sponsor: Hospices Civils de Lyon · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

Follicular lymphoma is the second most common adult B-cell lymphoma. The acquisition of the t(14;18) translocation is the genetic hallmark of Follicular lymphoma. However, 50% to 70% of healthy individuals harbor low levels of circulating t(14;18)-positive cells but will never develop Follicular lymphoma. It was observed that individuals who developed Follicular lymphoma showed a higher t(14;18) frequency than controls (Roulland et al., J Clin Oncol 2014). High t(14;18) frequency in blood from healthy individuals could be a predictive biomarker for Follicular lymphoma development. Genetic instability of those t(14;18)+ B-cells as well as failure of the micro-environment to control the proliferation of these cells are proposed mechanisms linking these lymphoma precursors to true lymphoma cells. The prognosis of Follicular lymphoma patients has been significantly improved mainly with the development of anti-CD20 monoclonal antibodies, with a current median overall survival over 15 years. However, this lymphoma remains an incurable disease. The most commonly used tool for prognostication of patients with Follicular lymphoma is the Follicular Lymphoma International Prognostic Index (FLIPI) based on conventional clinical and pathology parameters. Although it has clinical utility, the Follicular Lymphoma International Prognostic Index does not reflect the biologic heterogeneity of Follicular lymphoma. First-degree relatives of Follicular lymphoma had a fourfold increased risk of Follicular lymphoma suggesting a genetic etiology. Using the Genome wide association studies (GWAS) approach on Follicular lymphoma cohorts of 1,565 patients, the project plan to identify new prognostic markers. These markers will then be analyzed to decipher the impact of host genetics on somatic alterations and tumor biology, using public or matched patient data. The investigators also plan to analyze the influence of single-nucleotide polymorphisms on circulating t(14;18) levels in 318 healthy individuals included in EPIC cohort that will develop Follicular lymphoma later on, and assess if these biomarkers are helpful to refine the identification of high-risk Follicular lymphoma individuals.

Conditions

• Follicular Lymphoma
• Genetic Predisposition to Disease

Interventions

Type	Name	Description
GENETIC	Genome Wide Association Studies	Using the Genome wide association studies (GWAS) approach on these 1,565 patients, the project plan to identify new prognostic markers. These markers will then be analyzed to decipher the impact of host genetics on somatic alterations and tumor biology, using public or matched patient data.
GENETIC	Single-nucleotide polymorphisms's genotyping	Analyze of the influence of single-nucleotide polymorphisms on circulating t(14;18) levels

Timeline

• Start date: 2017-11-01
• Primary completion: 2019-07-01
• Completion: 2019-11-01
• First posted: 2017-07-31
• Last updated: 2017-07-31

Locations

1 site across 1 country: France